This project is a follow-up study to examine in detail the cellular and molecular lesions during the development of primary human liver cancer in order to define the histogenesis of this disease. Particular emphasis will be placed on defining the possible role of the hepatic stem cell compartment in hepatocarcinogenesis and possible other chronic liver diseases. It has been established that increased serum alpha-fetoprotein with fluctuating patterns is predictive of significant risk for development of hepatocellular carcinoma. It has also been shown that increased serum alpha-fetoprotein is a reflection of active proliferation of the hepatic stem cell compartment. The proposed study will provide information on the relationship between the hepatic stem cells and tumor development in the liver not generally obtainable in other investigations. The data obtained from this study will help the National Cancer Institute's Laboratory of Experimental Carcinogenesis to determine whether the hepatic stem cells are progenitors for human hepatocellular carcinoma. All appropriate clearances have been obtained. The contract with the Chinese Academy of Medical Sciences was determined to be in the best interest of the Government in accordance with the attached copy of the JOFOC.